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Continuous monitoring of blood sugar (glucose) in premature infants leads to better control than the standard approach of intermittent testing, a new study found. Research suggests it could prevent serious health and developmental problems in the infants. 

In standard intensive care for newborns (neonatal care), babies need to have their blood sampled every few hours. Staff take a reading of blood glucose and adjust treatment to keep levels steady. With continuous glucose monitoring (CGM), a sensor is inserted under the skin, and it monitors glucose levels constantly. The sensor can alert healthcare professionals when glucose levels are too high or too low. 

Continuous glucose monitoring (CGM) is already used to monitor children with diabetes and in some adult intensive care units. But before this study, it had not been tested in a trial of premature infants. 

The new work showed that CGM was more effective at keeping blood sugar levels steady compared to the standard clinical approach. Staff used the trends in glucose concentration to guide treatment, which avoided large swings in sugar levels. This is important because high, low or unstable glucose levels in premature infants are associated with poor outcomes and an increased risk of death. 

CGM devices are not yet designed for premature infants. The researchers hope that devices will be developed specifically for very small babies.  

Further information about the care of ill or premature babies is available on the NHS website

What’s the issue?

A baby born before week 37 of pregnancy (3 weeks earlier than full pregnancy) is premature. Those born before 28 weeks are extremely preterm and usually require care in special newborn (neonatal) units.

High, low or unstable blood sugar (glucose) levels are common in premature infants, especially those who are extremely preterm. They are linked to developmental problems during childhood, and an increased risk of a range of health problems including brain bleeds, problems with the eyes or gut, and changes to brain structure. Premature infants with fluctuating blood glucose levels are more likely to die. 

Keeping premature infants’ blood sugar at a constant level is challenging. Attempts to address high glucose levels can result in them falling quickly and becoming too low. In addition, very premature infants should be handled as little as possible. Standard care means staff taking blood samples every few hours to test glucose levels. Current measurements are therefore taken as infrequently as possible, and the amount of blood taken is kept to a minimum. But this cannot always protect infants against extreme blood sugar levels. 

CGM is already used for adults and children with diabetes and in some adult intensive care units. However, no device has been designed specifically for premature babies. The study explored whether these devices are safe to use in premature infants.

What’s new?

The study included premature infants, born between 23 and 34 weeks’ gestation. They were born at 13 centres in the UK, Spain and the Netherlands. They were randomly assigned to have their glucose levels managed either according to standard care or with the support of CGM. They were studied in their first days of life, when most fluctuations in blood glucose levels occur.

Infants in the standard care group had a CGM device inserted but staff did not receive data from it, whereas staff could use CGM data in real time to guide care of infants in the CGM group. 

Researchers analysed data on 70 infants in the CGM group, and 85 who received standard care. They looked at the length of time infants spent with a glucose level within the target range (between 2.6 – 10mmol/L).

In their first 6 days of life, infants in the CGM group spent, on average, more time with their glucose level in the target range:

    • infants in the CGM group spent 135 of 144 hours in the target range (94% of the time)
    • infants receiving standard care spent 121 of 144 hours in the target range (84% of the time).

Infants in the CGM group were less likely to have their glucose level drop below the target range (<2.6mmol/l) for more than an hour:

    • 4 out of 70 infants with CGM (6%) had this drop in glucose levels
    • 13 out of 85 infants on standard care (15%) had this drop in glucose levels. 

No infant had a serious adverse reaction to the CGM device and there were no serious episodes of infection in the study. CGM did not interfere with infant care or cause any distress. Most parents (80%) and staff (70%) thought that CGM improved clinical care.

However, the CGM device is not specifically designed for very small babies, and its use was a challenge. More babies with CGM than with standard care dropped out of the study. Data could not be collected from:  

    • 15 of an original 85 infants (17%) with CGM 
    • 10 of an original 95 infants (11%) on standard care.

Why is this important?

With current standard practice, measurements are taken infrequently, and may miss times when infants have high or low blood glucose. Previous work has shown that infants with high or low blood glucose may not show any signs to indicate a problem. These so-called ‘silent episodes’ are linked with worse outcomes in childhood. 

CGM increases the time that premature infants spend with blood sugar levels in the target range. Staff can alter treatment quickly and avoid dramatic swings in glucose levels. This could improve infants’ long-term health. In addition, CGM means that infants need fewer painful blood tests.  

This multicentre study shows that CGM can be helpful in a range of neonatal units. 

What’s next?

The CGM device was not designed for premature infants. It failed to give readings for some babies so there was no data to include in the analysis. However, the team found that insertions were easier with practice. The study provided the opportunity to learn techniques to support the better use of CGM in these babies. The researchers hope that manufacturers will now look to design CGM devices specifically for premature infants.

The work also indicated that CGM was cost-effective. The neonatal unit in Cambridge, UK, has made CGM standard practice for extremely preterm infants. Other units that took part in the research are also planning to make this change.

Existing guidelines suggest that the target range for glucose levels is between 2.6 – 10mmol/L. But further work is needed to establish whether this is the optimal glucose target for babies. The impact of glucose levels on longer term outcomes should also be explored. CGM will be important in providing the data to support this work.

The research suggested that severe gut inflammation (necrotising enterocolitis) might be more common with standard care. However, the study was not large enough to say for certain. The team recommends further research in this area.

You may be interested to read

This NIHR Alert is based on: Beardsall K, and others. Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomized controlled trial. Lancet Child & Adolescent Health 2021;5:265-73

Research on blood glucose concentrations in premature infants: Li T, and others. Glucose monitoring and management in the NICU – how are we doing? Infant Journal 2017;13:182-186

Further research on using CGM in neonatal units: Beardsall K. Real time continuous glucose monitoring in neonatal intensive care. Early Human Development 2019:138:104844

A cost-effectiveness analysis of using CGM in preterm infants: Petrou S, and others. Cost-effectiveness of real time continuous glucose monitoring to target glucose control in preterm infants. Seminars in Perinatology 2021;45:151392

 

Funding: The study was funded by the  NIHR Efficacy and Mechanisms Evaluation Programme. 

Conflicts of Interest: The study authors declare no conflicts of interest.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.


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Commentaries

Study author

This was a challenging study to perform for a number of reasons, and I was relieved and excited by the results. We had to recruit within 24 hours of birth, which was difficult. Also, many of the units taking part in the study had no experience with CGM and needed a lot of support.Showing that CGM is an improvement on standard care is exciting and could make a difference for premature babies.Kathy Beardsall, Department of Paediatrics, University of Cambridge 

Member of the public

As a former preterm infant myself, I have heard of the adverse effects of very high or low glucose levels in premature infants. I am confident that CGM can improve glucose control in neonatal units. Parents viewed their infants’ care more positively when CGM was used, which could possibly reduce their stress levels.Since blood sampling can cause stress in premature infants, reducing sample numbers is important. Until monitoring devices are designed for premature infants, implementing the findings will be difficult and require a lot of training for staff.Using CGM in preterm infants has the potential to make a big impact in their neonatal development and the potential to reduce healthcare costs later in life.G Miller, Public Contributor, Gloucester 

Paediatrician  

The use of CGM is well established in children with diabetes. It allows earlier detection and prevents exposure to extreme swings in blood glucose. There is strong evidence that it is better than the finger-prick test in picking up low blood glucose levels in children who have recurrent silent episodes of low blood glucose that they are unaware of.This paper widens the scope for CGM in the UK to include preterm infants. My own work suggests it should also be provided for children who do not have diabetes but have recurrent hypoglycaemia because of congenital hyperinsulinism (high levels of insulin) and metabolic disorders. Using CGM more widely could allow us to better manage the blood glucose concentrations of babies and children. It could reduce the risk of death and of long-term health conditions.Funding pathways for access to CGM need to be looked at urgently. They are complex and highly variable, determined locally by Clinical Commissioning Groups. National guidelines currently exclude children without a diagnosis of diabetes from accessing CGM. This is a health inequality which could be an obstacle to implementing these findings.May Ng, Associate Professor, University of Liverpool and Consultant Paediatric Endocrinologist, Southport and Ormskirk Hospital NHS 
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